Reprogrammed stem cells could cause cancer

Kate Taylor, 21st February 2011

The use of reprogrammed stem cells for medical treatments is looking doubtful, with the discovery that such cells can lead to genomic abberations which could cause cancer.

The discovery will come as a blow to those who believe that three-day-old embryos are people - or, rather, to those whose life depends on the development of stem cell treatments.

It had been hoped that ordinary stem cells reprogrammed into a 'pluripotent' state - meaning they can grow into any type of cell, just like an embryonic stem cell - could sidestep ethical issues over the use of embryonic cells.

"The recent discovery of the 'reprogramming' phenomenon, by which somatic cells can be induced to convert to a pluripotent state simply by forcing the expression of a few genes, opens a phenomenal number of possibilities in regenerative medicine," says Didier Trono, Dean of the EPFL School of Life Sciences.

"Imagine, for example, collecting a few cells from the hair follicle of a hemophiliac patient, reprogramming them to the pluripotentiality of their embryonic precursor, correcting the mutation responsible for the coagulation disorder that plagues the patient, and then re-administering them, genetically 'cured', after having orchestrated a differentiation into fully functional progeny."

But a new study from Trono's lab, along with the Department of Biochemistry at the University of Geneva and the European Institute of Oncology in Milan, has found that these reprogrammed cells exhibit a genomic instability that appears to be caused by the process used to return the cells to their embryonic state.

Even more seriously, the mutations observed resemble those that are found in cancer cells. The scientists draw the conclusion that reprogrammed stem cells need to be extensively investigated before they can even be considered for use in regenerative medicine.

The experiments were carried out using mouse mammary and fibroblast cells.

The researchers used three different processes for reprogramming the cells to an embryonic state. The first method was developed expressly for this study, and the others have already been well documented.

All three led to the same result: the genetic anomalies multiplied, in a way that seems to indicate that they're inherent to the reprogramming process itself, which typically makes use of oncogenes.

"Interestingly, oncogenes have the potential to induce genomic instability," the authors explain, saying that more work will be needed to establish whether there's any way round the problem.